开发浓度控制的连续纳米沉淀法来制备高载药量的脂质纳米颗粒,Aggregate

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开发浓度控制的连续纳米沉淀法来制备高载药量的脂质纳米颗粒
Aggregate ( IF 13.9 ) Pub Date : 2023-06-17 , DOI: 10.1002/agt2.369
Letao Xu _{1,

2} , Xing Wang ₂ , Guangze Yang ₂ , Zihan Zhao ₂ , Yilun Weng ₁ , Yang Li _{1,

2} , Yun Liu ₂ , Chun‐Xia Zhao _{1,

2}

Affiliation

基于脂质的纳米结构在过去二十年中引起了人们的广泛兴趣，并取得了巨大的临床成功，包括 1995 年首次临床批准用于癌症治疗的脂质体 (Doxil) 和最近的 COVID-19 mRNA 脂质纳米颗粒疫苗。与具有围绕水性核心的脂质双层的脂质体相比，具有颗粒结构的脂质纳米颗粒对于包封水溶性差的药物具有许多吸引人的优点，例如由于颗粒结构而具有更好的稳定性，由于预包封或预包封而具有较高的药物包封效率。联合载药策略。尽管许多研究报道了用于疏水性药物封装的脂质纳米粒子的合成，但药物负载和封装效率的精确控制仍然是一个重大挑战。这项工作报告了一种新的浓度控制纳米沉淀平台技术，用于制造载药量可调至 70 wt% 的脂质纳米颗粒。该方法适用于包封从非常疏水性到轻微亲水性的多种药物。利用这种简便的方法，载药量可调的纳米颗粒表现出优异的性能，如粒径小、尺寸分布窄、颗粒稳定性好，在未来的药物输送应用中显示出巨大的前景。

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Development of a concentration-controlled sequential nanoprecipitation for making lipid nanoparticles with high drug loading

Lipid-based nanostructures have garnered considerable interests over the last two decades, and have achieved tremendous clinical success including the first clinical approval of a liposome (Doxil) for cancer therapy in 1995 and the recent COVID-19 mRNA lipid nanoparticle vaccines. Compared to liposomes which have a lipid bilayer surrounding an aqueous core, lipid nanoparticles with a particle structure have several attractive advantages for encapsulating poorly water-soluble drugs such as better stability due to the particle structure, high drug encapsulation efficiency because of a pre- or co-drug-loading strategy. While many studies have reported the synthesis of lipid nanoparticles for hydrophobic drug encapsulation, the precise control of drug loading and encapsulation efficiency remains a significant challenge. This work reports a new concentration-controlled nanoprecipitation platform technology for fabricating lipid nanoparticles with tunable drug loading up to 70 wt%. This method is applicable for encapsulating a wide range of drugs from very hydrophobic to slightly hydrophilic. Using this facile method, nanoparticles with tunable drug loading exhibited excellent properties such as small particle size, narrow size distribution, good particle stability, showing great promise for future drug delivery applications.

更新日期：2023-06-17

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